Toll-like receptor 2 antagonists identified through virtual screening and experimental validation

Prasannavenkatesh Durai, Hyeon Jun Shin, Asma Achek, Hyuk Kwon Kwon, Rajiv Gandhi Govindaraj, Suresh Panneerselvam, Dhanusha Yesudhas, Jiwon Choi, Kyoung Tai No, Sangdun Choi

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


Toll-like receptor 2 (TLR2) antagonists are key therapeutic targets because they inhibit several inflammatory diseases caused by surplus TLR2 activation. In this study, we identified two novel nonpeptide TLR2 antagonists, C11 and C13, through pharmacophore-based virtual screening. At 10 μm, the level of interleukin (IL)-8 inhibition by C13 and C11 in human embryonic kidney TLR2 overexpressing cells was comparable to the commercially available TLR2 inhibitor CU-CPT22. In addition, C11 and C13 acted in mouse macrophage-like RAW 264.7 cells as TLR2-specific inhibitors and did not suppress the tumor necrosis factor-α induction by TLR3 and TLR4 activators. Moreover, the two identified compounds bound directly to the human recombinant TLR2 ectodomain, during surface plasmon resonance analysis, and did not affect cell viability in a 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethonyphenol)-2-(4-sulfophenyl)-2H-tetrazolium assay. In total, two virtually screened molecules, C11 and C13, were experimentally proven to be effective as TLR2 antagonists, and thus will provide new insights into the structure of TLR2 antagonists, and pave the way for the development of TLR2-targeted drug molecules.

Original languageEnglish
Pages (from-to)2264-2283
Number of pages20
JournalFEBS Journal
Issue number14
Publication statusPublished - 2017 Jul 1

Bibliographical note

Publisher Copyright:
© 2017 Federation of European Biochemical Societies

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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